Preventive and/or therapeutic agent for viral infection

ABSTRACT

To provide a novel preventive and/or therapeutic agent against a virus, disclosed is a preventive and/or therapeutic agent against a viral infection containing geranyl-geranyl acetone as an active ingredient. Also, disclosed are inducers for increasing the activity of an anitiviral factor and for protein kinase containing geranyl-geranyl acetone as an active ingredient. Moreover, a method for preventing and/or treating a viral infection which contains administering a patient a effective amount of an agent containing geranyl-geranyl acetone as an active ingredient.

TECHNICAL FIELD

[0001] The present invention relates to a new use of geranyl-geranylacetone as a preventive and/or therapeutic agent, and more particularlyto the preventive and/or therapeutic agents for viral infectioncontaining geranyl-geranyl acetone as an active ingredient.

BACKGROUND ART

[0002] Viruses cause a variety of illnesses. For example, influenza Aviral infection involves one type of virus that causes group infectionand epidemics around the world, and that often presents severeconditions for children, the elderly, and persons with cardiopulmonarydiseases or immunodeficiency. (Refer to non-patent literatures 1 to 3.).

[0003] No reliable and effective remedy for viruses has yet beendiscovered during the development in recent years of various drugs.Currently, although inoculation with inactive vaccine has been used asan effective means, the influenza A virus, for example, has effectivelyaltered its superficial antigenicity, and the therapeutic effectivenessof the vaccine is often reduced.

[0004] There have been many recent reports on the in vivo or in vitroeffectiveness of chemotherapy on viral infections when using the newdrugs zanamivir and oseltamivir (Refer to Non-Patent Literature 4through 8.), which are neuraminidase inhibitors, as well as drugs suchas amantazine and rimantadine, which are ion channel blockers.

[0005] However, there have been reports (Refer to Non-Patent Literature9.) that these are only effective when administered during earlyinfection, and cannot prevent pneumonia and secondary infection, andresistant viruses have been reported.

[0006] In this regard, heat shock protein (hereinafter referred to“HSP”) belongs to the group of stress proteins induced in the cell undervarious kinds of stress, and the most notable phenomenon in this area isa heat shock protein with a molecular weight of 70 kD (hereinafterreferred to “HSP70”). Recently, a wealth of research has focused on thistopic, and there have been many reports of the protective effects ofheat shock protein in relation to the living body and cells.

[0007] HSP has an anti-inflammatory action in relation tolipopolysaccharides, suppresses inflammatory cytokine, has an effect toprotect from ischemia, and suppresses cellular apoptosis, therefore,from the perspective of protecting the body from attack, HSP showspromise for treating a variety of diseases such as septic shock, andischemic conditions of vital organs such as the heart and brain.

[0008] However, there is no practical method to induce HSP for clinicalapplications, since the induction is based on the environmental stresssuch as heat shock, sodium arsenate and heavy metals, or on the diseasestress such as ischemia. No method to safety induce HSP in the body hasyet been established.

[0009] In recent years, there have been reports that the mechanism ofaction of geranyl-geranyl acetone (hereinafter referred to “GGA”.Product name “Selbex”, manufactured by Eisai Co., Ltd.) is mediatedthrough the induction and expression of HSP. (Refer to Non-PatentLiterature 10.) For this reason, GGA is gaining notable attention as aclinically applicable HSP inducer.

[0010] Thus, an object of the present invention is to provide a new drugfor viruses by focusing on the strong HSP inductive action of GGA, andby studying the infection preventive and therapeutic effects in relationto viruses. Non-Patent Literature 1: Glezen WP. Epidemiol Rev. 1982; 4:25-44; Non-Patent Literature 2: Couch RB, Kasel JA, Glezen WP, et al. J.Infect Dis. 1986; 153: 431-40; Non-Patent Literature 3: MMWR Morb MortalWkly Rep 1997; 46(RR-9); 1-25; Non-Patent Literature 4: Woods JM,Bethell RC, Coates JA, et al. Antimicrob Agents Chemother 1993; 37:1473-9; Non-Patent Literature 5: Hayden FG, Osterhaus ADME, Treanor JJ,et al. N Engl J Med 1997; 337: 874-80; Non-Patent Literature 6: GubarevaLV, Kaiser L, Hayden FG, Lancet 2000; 355(9206), 827-35; Non-PatentLiterature 7: Long JK, Mossad, Goldman MP, Cleve Clin J Med 2000; 67:92-5; Non-Patent Literature 8: Wingfield WL, Pollack D, Grunert RR, NEngli J Med 1969; 281: 579-84; Non-Patent Literature 9: Wingfield WL,Pollack D, Grunert RR, N Engli J Med 1969; 281: 579-84; Non-PatentLiterature 10: Hirakawa T, Rokutan K, Nikawa T, et al. Gastroenterogy1996; 111: 345-57.

DISCLOSURE OF INVENTION

[0011] The above object is achieved by a preventive and/or therapeuticagent for a viral infection comprising geranyl-geranyl acetone as anactive ingredient.

[0012] In a preferable aspect of the present invention, according to theaforementioned preventive and/or therapeutic agent for viral infection,the viral infection is influenza viral infection.

[0013] The aforementioned object is also achieved by a preventive and/ortreat method for viral infection comprising administering to a patientan effective amount of a drug comprising geranyl-geranyl acetone as anactive ingredient

[0014] The aforementioned object is also achieved by use ofgeranyl-geranyl acetone for the manufacture of a preventive and/ortherapeutic agent for viral infection.

[0015] Further, the aforementioned object is achieved by an antiviralfactor activity enhancer comprising geranyl-geranyl acetone as an activeingredient.

[0016] In a preferable aspect of the present invention, according to theantiviral factor activity enhancer, the antiviral factor is MxA.

[0017] Moreover, the aforementioned object is achieved by a proteinkinase inducer comprising geranyl-geranyl acetone as an activeingredient.

[0018] In a preferable form of the present invention, according to theprotein kinase inducer, the protein is an interferon-inducibledouble-stranded RNA activated protein.

[0019] According to the present invention, GGA has the effect ofpreventing viral infection when pre-administered prior to infection by avirus, and has the effect of treating viral infection when administeredafter infection.

[0020] In addition, according to the present invention, administrationof GGA results in an increase of the expression of MxA, which is anantiviral gene, and results in an increase of the mRNA expression ofinterferon-inducible double-stranded RNA activated protein kinase.

BRIEF DESCRIPTION OF DRAWINGS

[0021]FIG. 1 indicates an improvement trend of clinical infectionsymptoms caused by administration of GGA in a mouse PR8 infection modelaccording to the present invention. BALC/c mice that used in the presentinvention were randomly allotted into the following 4 groups: {circleover (1)} Control group (n=30) is transnasally administered 2×10⁵ PFU ofA/PR/8/34; the GGA pre-treatment groups were orally administered GGAevery 12 hours for 3 weeks in doses of: {circle over (2)} 150 mg/kg(150G-PR8 group; n=30), {circle over (3)} 75 mg/kg (75G-PR8 group;n=30), {circle over (4)} 15 mg/kg (15G-PR8 group; n=30) and wereinfected with PR8 after 3 weeks in the same manner. The body weights ofthe mice were measured 1, 2, 3, 4, 7, and 10 days after infection;

[0022]FIG. 2 indicates the effects of GGA on viral replication in thelungs of the mice of the various groups after infection by influenzaviruses according to the present invention;

[0023]FIG. 3 indicates the effects of GGA on viral nucleoproteinsynthesis in the lungs of mice in the various groups after infection byan influenza virus according to the present invention. Further, the 150mg/kg GGA, 75 mg/kg GGA, and 15 mg/kg GGA in FIG. 3 indicate the150G-PR8 group, 75G-PR8 group and 15G-PR8 group respectively;

[0024]FIG. 4 indicates the effects of GGA on viral nucleoproteinsynthesis in the lungs of mice in the various groups after infection byPR8 according to the present invention, and the results of assay usingEIA;

[0025]FIG. 5 indicates the results of expressing HSP70 in the lungs ofmice administered GGA according to the present invention;

[0026]FIG. 6 indicates the effects of GGA on the dynamics of HSP70 mRNAexpression in the lungs of mice after infection by PR8 according to thepresent invention, and the results of northern blot assessment. Further,the 150 mg/kg GGA, 75 mg/kg GGA, and 15 mg/kg GGA in FIG. 6 indicate the150G-PR8 group, 75G-PR8 group and 15G-PR8 group respectively;

[0027]FIG. 7 indicates the effects of GGA on HSP induction in A549 cellsderived from human lung epithelium, according to the present invention;

[0028]FIG. 8 indicates the results of using SDS-PAGE to developintracellular protein based on pulse labeling using ³⁵S-methionine inthe present invention;

[0029]FIG. 9 indicates the results of studying the effects of GGA on NPand HSP70 synthesis capacities during PR8 infection according to thepresent invention;

[0030]FIG. 10 indicates the results of densitometric analysis of theamount of protein in the samples studied in FIG. 9 at the various timesafter infection.

[0031]FIG. 11 indicates the results of western blot analysis of theaccumulation of HSP70 and nucleoprotein NP in cells 12 hours after PR8infection according to the present invention;

[0032]FIG. 12 indicates the effects of GGA treatment on the expressionof anti-virus genes during PR8 infection according to the presentinvention; and

[0033]FIG. 13 indicates the effects of GGA treatment on the expressionof anti-virus genes during PR8 infection according to the presentinvention.

BEST MODE FOR CARRYING OUT THE INVENTION

[0034] The present invention discovers firstly that administration ofGGA has an effect to prevent and treat infection by influenza viruses.The embodiment of the present invention will be described in detailbelow while explaining experiments conducted using the presentinvention.

[0035] The GGA used in the present invention has the generic name ofteprenone, and is widely used as a drug to treat stomach ulcers andstomach inflammation; it is also possible to acquire GGA as a reagent orindustrial raw material, and it can be synthesized using well-knownmethods of synthesis. The chemical name of GGA is 6, 10, 14,18-tetramethyl-5, 9, 13, 17-nonadecatetraen-2-one, and the structuralformula is as follows:

[0036] GGA has a double bond in 4 locations in its structure, and thereare a total of 8 geometric isomers. However, the present invention isnot particularly limited to one, and any one, or compounds of two ormore, of the isomers may be used. (5E, 9E, 13E)-6, 10, 14,18-tetramethyl-5, 9, 13, 17-nonadecatetraen-2-one, and (5Z, 9E, 13E)-6,10, 14, 18-tetramethyl-5, 9, 13, 17-nonadecatetraen-2-one may be citedas preferable compounds among these.

[0037] In the present invention, mouse infection models were used as invivo tests to study the trends in improving clinical infection symptoms,etc by administration of GGA. Specifically, groups are divided into aGGA pre-treatment group and a group without pre-treatment, and afterinfecting both groups with influenza virus, various types of behaviorwere observed in detail.

[0038] Further, influenza virus is used as a representative example of avirus, but the present invention is not limited to this, and includesviruses that cause flu such as the rhinovirus, and viruses that infectthe skin and mucous membranes such as the herpes virus, etc.

[0039] After infection by an influenza virus, the effects ofadministering GGA are analyzed using well-known methods such as plaqueassay, western blot, and northern blot from the perspective of theweights of the mice, viral replication in the lungs of the mice, viralnucleoprotein synthesis in the lungs of the mice, and expression ofHSP70.

[0040] According to the previously described analyses, reduced weightloss in the mice, the reduction of the viral count in the lungs of themice, the suppression of the amount of expression of virus nucleoproteinin the lungs of the mice, and the increased expression of HSP70 allindicates dependence on the concentration of GGA used for pre-treatment.Specifically, according to the present invention, the greater the doseof GGA in the group of mice pre-administered GGA, the less weight loss,and the results of finding no viral growth in the lungs indicate that itis possible to prevent viral infection by administering GGA in advance.

[0041] Next, in the present invention, human lung epithelial cells isused in in vitro experiments to study the presence of antiviral activitycaused by administration of GGA.

[0042] Using A549 cells as the previously described human lungepithelial cells, the effect of GGA treatment to induce HSP, thesynthesis capacity of nucleoproteins or HSP after infection by aninfluenza virus, and the expression of antiviral genes are assessed.

[0043] When treating with GGA according to the present invention, theexpression of HSP70 mRNA is induced in a manner dependent on theconcentration of GGA, and the synthesis capacity increases even at thelevel of protein material.

[0044] Even after infection with an influenza virus, GGA treatmentcauses strong expression of the HSP protein, and therefore, suppressesthe capacity to synthesize various types of viral proteins such asinfluenza blood coagulant protein, matrix protein and non-structuralprotein.

[0045] Further, in the present invention, from studying the effects onthe expression of anti-virus genes during infection with an influenzavirus after GGA treatment, the expression of HSP70 mRNA is enhanced, andthe expressions of MxA, which is an antiviral gene, andinterferon-inducible double-stranded RNA activate protein kinase, whichhas an antiviral action, is activated in A549 cells treated with GGA.Thus, this suggests the possibility that the present invention has anenhanced biological function to prevent and suppress viral infection inhost cells, and it may be inferred that the administration of GGA afterviral infection has the effect of treating viral infection.

[0046] Here, the dose of GGA could be suitably determined based on thetype of viral infection, symptoms, age, and body weight. Normally, thedaily dose for adults is from 150 mg to 3 g, and preferably, from 200 mgto 2 g, and more preferably, from 250 mg to 1.5 g.

[0047] The method of administering GGA is not particularly limited, andoral or non-oral administration can be suitably selected, but oraladministration is more preferable.

[0048] The form for oral administration may be a solid or liquidformulation, and specifically, a tablet, a coated tablet, a pill, asubtle granule, a granule, a powder, a capsule, a syrup, a emulsion, anda suspension are preferable. GGA is already widely used as a drug; thetoxicity is low; there are no known side effects. Thus, it is a highlysafe compound. Therefore, it may be orally administered as a powder.Alternatively, it may be made into a suitable formulation containing theadditives most commonly used in the field of formulation (for example,lactose, sucrose, starch, mannitol, etc.) and thinners, etc.

[0049] Further, according to need, the aforementioned drug may beadministered as a drug containing, in addition to GGA, an antioxidant, abinder (for example, α-starches, gum arabic, carboxymethyl cellulose,polyvinylpyrrolidone, and hydroxypropyl cellulose, etc.), adisintegrating agent (for example, calcium carbonate, and calciumcarboxymethyl cellulose, etc.), a lubricant (for example, talc,magnesium stearate, and polyethylene glycol 6000, etc.), a colorant, aflavoring agent, and a fragrance, etc.

[0050] A preferable form of the preparation for non-oral administrationinclude an injectable solution, a drip infusion preparation, an externalpreparation, and a suppository.

EXAMPLES

[0051] A further detailed description of the present invention will beprovided below by indicating examples, but the present invention is notlimited to these.

[0052] Further, the following experimental procedures relating to thehandling of test animals were conducted with the approval of the AnimalTesting Ethical Standards Committee of Oita Medical College.

[0053] The action of GGA in relation to the symptoms of viral infection,specifically, the infection rate and the death rate, in infection by anotable influenza virus was analyzed for in vivo and in vitro tests.

[0054] The virus used in the present invention was the influenza Avirus, A/PR/8/34 (H1 N1) strain (hereinafter referred to “PR8”); themice were 6-week old female SPF (specific pathogen-free) BALB/cN mice(Charles River Japan Co., Ltd.); and the cells were A549 cells derivedfrom human alveolar epithelial cell.

[0055] First, the aforementioned mice were raised in a cage for each 4mice under clean conditions and allowed free access to sterilized feedand water.

[0056] The mice were randomly divided into the following 4 treatmentgroups, and tested: {circle over (1)} Control group; intranasl infectionwith PR8 (2×10⁵ PFU) {circle over (2)} 150G-PR8; group; afteradministration of 150 mg/kg of GGA, infected with the same amount of PR8in the same manner as the control group; {circle over (3)} 75G-PR8group; after administration of 75 mg/kg of GGA, infected with the sameamount of PR8 in the same manner as the control group; {circle over (4)}15G-PR8 group; after administration of 15 mg/kg of GGA, infected withthe same amount of PR8 in the same manner as the control group. Theaforementioned group {circle over (1)} refers to the control group, andgroups {circle over (2)} to {circle over (4)} refer to the GGA treatedgroup prior to infection. The GGA treated groups were orallyadministered GGA every 12 hours for 3 weeks.

[0057]FIG. 1 indicates the results of the effects of GGA on weight losscaused by PR8 infection. In the mouse PR8 infection model, the followingobservations were made regarding the improvement of the clinicalsymptoms of infection based on the administration of GGA.

[0058] In the control group, weight loss reaching 30% was observed afterinfection. In contrast, in the GGA treated groups, except for the75G-PR8 group, almost no weight loss caused by infection was observed.

[0059]FIG. 2 indicates the effects of GGA on viral replication in thelungs of the mice of the various groups after infection by an influenzavirus according to the present invention. Here, the assay of virus inthe lung was conducted by plaque assay using MDCK. As can be seen inFIG. 2, the amount of PR8 virus in the lungs of the control group grewup to approximately 10³ times the amount of virus after initially beinginfected. On the other hand, the growth of virus in the lungs of the GGAtreated groups was suppressed in a GGA dose-dependent manner, and thevirus was completely eliminated after 3 days in the 150G-PR8 group, andafter 4 days in the 75G-PR8 group.

[0060]FIG. 3 indicates the results of the effects of GGA on viralnucleoprotein (called “NP” hereinafter) synthesis in the lungs of themice of the various groups after infection by an influenza virusaccording to the present invention. The amount of NP synthesis wasmeasured with Western blot analysis. Compared with the control group,GGA treated groups were observed to exhibit suppression of NP synthesisin a dose dependent manner. The p.i. day listed in FIG. 3 indicates thenumber of days post-infection by PR8.

[0061]FIG. 4 indicates the effects of GGA on viral NP synthesis in thelungs of the mice of the various groups after infection according to thepresent invention; and the results of conducting detailed assays usingEIA are also indicated. As can be evident in FIG. 4, compared with thecontrol group, which was not administered GGA, the capacity tosynthesize NP after infection with PR8 was notably reduced in the GGAtreated groups.

[0062] Next, it was confirmed whether or not GGA induced expression ofHSP70 mRNA in the lungs of the mice.

[0063]FIG. 5 indicates the expression of HSP70 in mice lungs induced byGGA. As is clear form FIG. 5, when administering GGA to BALB/c mice for3 weeks (GGA150 in FIG. 5 indicates that 150 mg/kg of GGA wasadministered every 12 hours for 3 weeks), northern blot assay revealsthat expression of HSP70 in the lungs was induced in a dose dependentmanner. Specifically, GGA treated groups induced HSP70 more than thecontrol group (corresponding to “-” in FIG. 5), and the greater the doseof GGA, the larger the amount of expression thereof.

[0064]FIG. 6 indicates the results of using northern blot to study theeffects of GGA on the dynamics of HSP70 mRNA expression in the lungs ofmice after infection. In the same manner as in FIG. 5, FIG. 6 revealsthat the amount of HSP70 expressed was dependent on the amount of GGAadministered. Further, the p.i. day listed in FIG. 6 means the number ofdays post-infection by PR8.

[0065]FIGS. 5 and 6 are diagrams indicating the results of theexpression of HSP70 in the lungs of the mice induced by administrationof GGA when using glutaraldehyde diphosphate dehydrogenase (GAPDH) as acontrol. In FIG. 5, a vehicle was administered using a diluentcontaining α-tocopherol in an amount equivalent to that of the variousdoses.

[0066] The results of FIGS. 5 and 6 reveal that the administration ofGGA alone caused expression of HSP70 mRNA in the lung tissues in a dosedependent manner; that compared with the control group after infection,the expression of HSP70 mRNA in the lungs of the GGA treated groupsincreased in agreement with the weight loss and viral reproductionperiods in FIGS. 1 and 2; and that the enhancement of expression agreedwith times of improvement in symptoms. This suggests that there is astrong correlative relationship between the expression of HSP70 and thesuppression of the influenza infection.

[0067] The analysis of in vivo tests is explained above, and now theresults of tests conducted in vitro will be explained below.

[0068]FIG. 7 indicates the results of treating A549 cells with GGA in invitro tests conducted according to the present invention. Specifically,the results indicated in FIG. 7 reveal that GGA has an HSP inductiveeffect in A549 cells derived from human lung epithelium. Further, anassay of HSP induction was conducted using the northern blot method.

[0069] As indicated in FIG. 7, in the same way as in vivo, when GAPDHwas controlled, the expression of HSP70 mRNA was induced in aconcentration and time dependent manner. Incidentally, α in FIG. 7indicates α-Tocophenrol.

[0070]FIG. 8 indicates the results of using SDS-PAGE to developintracellular protein based on pulse labeling using ³⁵S-methionine. Inthese results, GGA powerfully induced the expression of approximately 70kD proteins over 24 hours, and the capacity for synthesis at the levelof protein material was notably elevated. (Refer to the left side ofFIG. 8.) Moreover, when using western blot based on HSP70 antibodies toanalyze the same samples, these proteins were identified as HSP70 (Referto the right side of FIG. 8.), and the expression of HSP70 was measuredas the peak of the expression 6 hours after administering GGA.

[0071]FIG. 9 indicates the results of studying the effects of GGA on NPand HSP70 synthesis capacities during PR8 infection. The pulse labelingmethod was used to analyze the protein synthesis capacities of NP andHSP70 in A549 cells without GGA treatment (−) and in those with GGAtreatment (+). In GGA treatment (−), the synthesis of NP was notablyenhanced for 24 hours after infection. On the other hand, in GGAtreatment (+), an enhancement of HSP70 synthesis was observed in theearly period of infection, and synthesis of NP that matched a decline inHSP70 began after 12 hours. The synthesis capacity was suppressedcompared to that of GGA treatment (−).

[0072]FIG. 9 also demonstrates that the capacity to synthesize viralproteins of PR8 such as HA (influenza hemagglutinin protein), NP, M1(matrix protein), and NS1 (non-structural protein) was notablysuppressed compared to the control. The suppression effect had a strongcorrelation with the time of expression of HSP70.

[0073]FIG. 10 indicates the results of densitometric analysis of theamount of protein in the samples studied in FIG. 9 at 3, 6, 12, and 24hours after infection. The results of FIG. 10 reveal that HSP70 wasexpressed up to 12 hours after PR8 infection.

[0074]FIG. 11 indicates the results of western blot analysis of theaccumulation of HSP70 and NP protein in cells 12 hours after PR8infection according to the present invention. These results reveal no NPsynthesis in the mock uninfected with virus. GGA treatment inducedHSP70, the expression of NP was prevented up to 12 hours afterinfection, and viral protein synthesis was notably suppressed bysynthesis of HSP70.

[0075] Studied next were the effects of GGA treatment on the expressionof antiviral genes after infection by PR8, and the results are indicatedin FIGS. 12 and 13. In FIG. 12, northern blot analysis reveals that GGAtreatment of A549 cells after infection with PR8 not only enhanced theexpression of HSP mRNA, but also enhanced the expression of MxA genes,which are antiviral genes (specifically, orthomixovirus). It should benoted that the GAPDH in FIG. 12 was used as a control in the same way aspreviously described in FIG. 5.

[0076]FIG. 13 indicates the results of using RT-PCR to assay the mRNAexpression of interferon-inducible double-stranded RNA activated proteinkinase (hereinafter referred to “PKR”), which has an antiviral action.The results demonstrate that GGA treatment enhanced expression of PKR inA549 cells, and also up-regulates that mRNA. It should be noted thatβ-actin in this diagram was used was a control.

[0077] Generally, when viral infection occurs, the expression of avariety of genes, antiviral factors and enzymes in the body are enhancedor suppressed. From the perspective of mechanisms of action, the factthat GGA acting on MxA gene and PKR strongly suggests that GGA will beeffective in the prevention and treating of viral infections,specifically, of influenza viruses. At the same time, it has beenindicated that GGA is an antiviral factor activity enhancer or a proteinkinase inducer.

[0078] The above results indicate that GGA exhibits an action tosuppress growth of influenza viruses in vivo, and causes notableimprovement of clinical symptoms such as weight loss. This suggests thatGGA-induced HSP70 in the lungs deeply participates in that effect.

[0079] Moreover, it was demonstrated that GGA strongly inducedexpression of HSP70 in vitro, and that the period of this inductioncoincided with the inhibited replication of the influenza virus.Further, it was found that GGA activates host side antiviral gene MxAand PKR during viral infection, and enhanced the capacity of livingbodies to prevent or suppress host viral infection. It was demonstratedthat the administration of GGA is effective as prevention or as remedyfor influenza viruses.

INDUSTRIAL APPLICABILITY

[0080] According to the above explanation, as a new use, geranyl-geranylacetone may be applied as a preventive and/or therapeutic agent forviral infections.

We claim:
 1. A preventive and/or therapeutic agent for a viral infectioncomprising geranyl-geranyl acetone as an active ingredient.
 2. Thepreventive and/or therapeutic agent for the viral infection according toclaim 1, wherein the virus is an influenza virus.
 3. A method ofpreventing and/or treating a viral infection comprising administering apatient an effective amount of a drug comprising geranyl-geranyl acetoneas an active ingredient.
 4. A use of geranyl-geranyl acetone for themanufacture of a preventive and/or therapeutic agent for a viralinfection.
 5. An antiviral factor activity enhancer comprisinggeranyl-geranyl acetone as an active ingredient.
 6. The antiviral factoractivity enhancer according to claim 5, wherein the antiviral factor isa MxA gene.
 7. A protein kinase inducer comprising geranyl-geranylacetone as an active ingredient.
 8. The protein kinase inducer accordingto claim 7, wherein the protein is interferon-inducible double-strandedRNA activated protein.